Clinical Analysis Of Different Therapeutic Modes Of TKI Combined With SRS In The Treatment Of Lung Adenocarcinoma Patients With EGFR Sensitive Mutation And Primary Brain Metastasis

Purpose:This study aimed to evaluate the superior timing to use epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs)and stereotactic radiosurgery(SRS)for primary brain metastases(BM)in patients with EGFR mutant non-small cell lung cancer(NSCLC).Methods:We performed a retrospective analysis of 92 patients from two institutions with EGFR-mutant NSCLC who had brain metastases at primary diagnosis.Patients were treated with SRS combined EGFR-TKI at the first line,or SRS following first-line EGFR-TKI at intracranial progression.Overall survival(OS),intracranial progression-free survival(iPFS)and extracranial progression-free survival(exPFS)were measured from the time of brain metastases.The prognostic factors that affected these patients were analyzed using the univariate and multivariate analysis by Kaplan-Meier methods and Cox regression models.Results:Among the 92 EGFR-mutant NSCLC patients with primary brain metastasis,66 were treated with first-line SRS combined EGFR-TKI(First-line Group)and 26 with SRS following first-line EGFR-TKI at intracranial progression(Progressive Group).The iPFS of the first-line group was shorter than the progressive group(18.3 vs.32.1m,p=0.018).There was no significant difference between OS and exPFS.A total of 131 brain metastases were measured,including 95 lesions in the first-line group and 36 lesions in the progressive group.We found that the intracranial objective remission rate(IORR)(56(58.9%)vs.13(36.1%),p=0.019)and intracranial disease control rate(IDCR)(88(92.6%)vs.27(75.0%),p=0.014)of the first-line group was higher than the progressive group.Further subgroup analysis showed that for asymptomatic patients(22.1 vs.33.4m,p=0.037),non-isolated BM(2-5 brain metastases)patients(14.0 vs,27.5m,p=0.009)and patients with EGFR exon 19 deletion(24.3 vs.37.0m,p=0.039),the iPFS in the progressive group was longer and the differences were statistically significant(p<0.05).Conclusion:In the local control of brain metastases,the IORR and IDCR of the first-line combination group were higher than those of the progressive group,and the differences were statistically significant.There were no significant differences in OS and exPFS between the first-line group and the progressive group,but the progressive group obtained better iPFS,especially in patients without brain metastasis-related symptoms,2-5 brain metastases and EGFR exon 19 deletion.The best time for radiotherapy needs to be confirmed by further prospective,large sample and long follow-up studies.